Human babesiosis is an emerging tick-borne disease in the US. babesiosis is a potentially life- threatening disease caused by apicomplexan piroplasm parasites that infect red blood cells (RBCs). In the U.S., babesiosis is primarily caused by Babesia microti (Bm), with some infections attributed to B. duncani (Bd) or a B. divergens-like strain MO1 (MO1). New treatments capable of rapid and complete clearance of parasites during human babesiosis are urgently needed. Tafenoquine (TQ) is a new 8- aminoquinoline drug for the prevention of relapse from liver hypnozoites of Plasmodium vivax. The goal of the current proposal is to complete preclinical animal studies to determine if TQ can be repurposed for human babesiosis; particularly for those patients who are immunocompromised for whom short-term or rapidly effective treatment options do not currently exist. The application of tafenoquine as a single dose therapy for immunocompromised patients with babesiosis would be a revolutionary development in our ability to treat babesiosis. In aim 1 we will test they hypothesis that tafenoquine leads to a radical cure for experimental babesiosis meaning that it eliminates parasites in immune-compromised mice. In aim 2 we will examine the mechanism of action of tafenoquine against Babesia.